MMS is an alkylating agent with a distribution of preferred sites of methylation of nucleic acid bases quite different from that of several other monofunctional methylators, and in cellular systems MMS has always required the operation of an "error-prone repair system" to be mutagenic. In phage T4, however, MMS displays a dual mechanism, acting partly through the viral WXY error-prone repair system and partly independently of that system. WXY-dependent mutagenesis produces frameshifts and a variety of base-pair substitutions, as do other mutagens acting through this system (such as UV and gamma radiations). WXY-independent MMS mutagenesis produces mutations only at G:C base pairs, and these probably consist of transitions. The second mechanism is consistent with the observed (but infrequent) guanine-06 methylation by MMS, and the differences between phage T4 and cellular systems is consistent with a progressive increase in DNA polymerase discrimination associated with progressive decreases in mutability with increasing genome size.